Closed loop impedance-based cardiac resynchronization therapy systems, devices, and methods

ABSTRACT

This document discusses, among other things, systems, devices, and methods measure an impedance and, in response, adjust an atrioventricular (AV) delay or other cardiac resynchronization therapy (CRT) parameter that synchronizes left and right ventricular contractions. A first example uses parameterizes a first ventricular volume against a second ventricular volume during a cardiac cycle, using a loop area to create a synchronization fraction (SF). The CRT parameter is adjusted in closed-loop fashion to increase the SF. A second example measures a septal-freewall phase difference (PD), and adjusts a CRT parameter to decrease the PD. A third example measures a peak-to-peak volume or maximum rate of change in ventricular volume, and adjusts a CRT parameter to increase the peak-to-peak volume or maximum rate of change in the ventricular volume.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No.11/136,894, filed May 25, 2005, the specification of which is hereinincorporated by reference.

TECHNICAL FIELD

This patent document pertains generally to cardiac function managementdevices, and more particularly, but not by way of limitation, to closedloop resynchronization therapy systems, devices, and methods.

BACKGROUND

When functioning properly, the human heart maintains its own intrinsicrhythm. Its sinoatrial node generates intrinsic electrical cardiacsignals that depolarize the atria, causing atrial heart contractions.Its atrioventricular node then passes the intrinsic cardiac signal todepolarize the ventricles, causing ventricular heart contractions. Theseintrinsic cardiac signals can be sensed on a surface electrocardiogram(ECG) obtained from electrodes placed on the patient's skin, or fromelectrodes implanted within the patient's body. The surface ECGwaveform, for example, includes artifacts associated with atrialdepolarizations (“P-waves”) and those associated with ventriculardepolarizations (“QRS complexes”).

A normal heart is capable of pumping adequate blood throughout thebody's circulatory system. However, some people have irregular cardiacrhythms, referred to as cardiac arrhythmias. Moreover, some patientshave poor spatial coordination of heart contractions. Some patients mayhave both irregular rhythms and poor spatial coordination of heartcontractions. In either of these cases, diminished blood circulation mayresult. For such patients, a cardiac function management system may beused to improve the rhythm and/or spatial coordination of heartcontractions. Such systems are often implanted in the patient anddeliver therapy to the heart, such as electrical stimulation pulses thatevoke or coordinate heart chamber contractions.

One problem faced by physicians treating cardiovascular patients is thetreatment of congestive heart failure (also referred to as “CHF”).Congestive heart failure, which can result from a number of causes suchas long-term hypertension, is a condition in which the muscle in thewalls of at least one of the right and (more typically) the left side ofthe heart deteriorates. By way of example, suppose the muscle in thewalls of left side of the heart deteriorates. As a result, the leftatrium and left ventricle become enlarged, and that heart muscledisplays less contractility. This decreases cardiac output of bloodthrough the circulatory system which, in turn, may result in anincreased heart rate and less resting time between heartbeats. The heartconsumes more energy and oxygen, and its condition typically worsensover a period of time.

In the above example, as the left side of the heart becomes enlarged,the intrinsic electrical heart signals that control heart rhythm mayalso be affected. Normally, such intrinsic signals originate in thesinoatrial (SA) node in the upper right atrium, traveling throughelectrical pathways in the atria and depolarizing the atrial hearttissue such that resulting contractions of the right and left atria aretriggered. The intrinsic atrial heart signals are received by theatrioventricular (AV) node which, in turn, triggers a subsequentventricular intrinsic heart signal that travels through specificelectrical pathways in the ventricles and depolarizes the ventricularheart tissue such that resulting contractions of the right and leftventricles are triggered substantially simultaneously.

In the above example, where the left side of the heart has becomeenlarged due to congestive heart failure, however, the conduction systemformed by the specific electrical pathways in the ventricle may beaffected, as in the case of left bundle branch block (LBBB). As aresult, ventricular intrinsic heart signals may travel through anddepolarize the left side of the heart more slowly than in the right sideof the heart. As a result, the left and right ventricles do not contractsimultaneously, but rather, the left ventricle contracts after the rightventricle. This reduces the pumping efficiency of the heart. Moreover,in LBBB, for example, different regions within the left ventricle maynot contract together in a coordinated fashion.

Cardiac function management systems include, among other things,pacemakers, also referred to as pacers. Pacers deliver timed sequencesof low energy electrical stimuli, called pace pulses, to the heart, suchas via an intravascular lead wire or catheter (referred to as a “lead”)having one or more electrodes disposed in or about the heart. Heartcontractions are initiated in response to such pace pulses (this isreferred to as “capturing” the heart). By properly timing the deliveryof pace pulses, the heart can be induced to contract in proper rhythm,greatly improving its efficiency as a pump. Pacers are often used totreat patients with bradyarrhythmias, that is, hearts that beat tooslowly, or irregularly. Such pacers may also coordinate atrial andventricular contractions to improve pumping efficiency.

Cardiac function management systems also include cardiacresynchronization therapy (CRT) devices for coordinating the spatialnature of heart depolarizations for improving pumping efficiency, suchas for patients having CHF. For example, a CRT device may deliverappropriately timed pace pulses to different locations of the same heartchamber to better coordinate the contraction of that heart chamber, orthe CRT device may deliver appropriately timed pace pulses to differentheart chambers to improve the manner in which these different heartchambers contract together, such as to synchronize left and right sidecontractions.

Cardiac function management systems also include defibrillators that arecapable of delivering higher energy electrical stimuli to the heart.Such defibrillators include cardioverters, which synchronize thedelivery of such stimuli to sensed intrinsic heart activity signals.Defibrillators are often used to treat patients with tachyarrhythmias,that is, hearts that beat too quickly. Such too-fast heart rhythms alsocause diminished blood circulation because the heart isn't allowedsufficient time to fill with blood before contracting to expel theblood. Such pumping by the heart is inefficient. A defibrillator iscapable of delivering a high energy electrical stimulus that issometimes referred to as a defibrillation countershock, also referred tosimply as a “shock.” The countershock interrupts the tachyarrhythmia,allowing the heart to reestablish a normal rhythm for the efficientpumping of blood. In addition to pacers, CRT devices, anddefibrillators, cardiac function management systems also include devicesthat combine these functions, as well as monitors, drug deliverydevices, and any other implantable or external systems or devices fordiagnosing or treating the heart.

The present inventors have recognized a need for improved techniques fordetermining the degree of asynchrony (also sometimes referred to asdyssynchrony) between the left and right sides of the heart of a CHFpatient.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, which are not necessarily drawn to scale, like numeralsdescribe substantially similar components throughout the several views.Like numerals having different letter suffixes represent differentinstances of substantially similar components. The drawings illustrategenerally, by way of example, but not by way of limitation, variousembodiments discussed in the present document.

FIG. 1 is a schematic diagram illustrating generally one example ofportions of a system and portions of an environment with which it isused.

FIG. 2 is a flow chart illustrating generally one example of a techniquefor determining a degree of synchrony or asynchrony between left andright ventricular contractions of a heart.

FIG. 3A is a conceptual (not real data) impedance vs. time graph of RVZand LVZ over the same cardiac cycle for the case of synchrony betweenright and left ventricular contractions.

FIG. 3B is a conceptual (not real data) impedance vs. time graph of RVZand LVZ over the same cardiac cycle for the case of mild asynchronybetween right and left ventricular contractions.

FIG. 3C is a conceptual (not real data) impedance vs. time graph of RVZand LVZ over the same cardiac cycle for the case of severe asynchronybetween right and left ventricular contractions.

FIG. 4A is a graph (corresponding to FIG. 3A) of right ventricularimpedance (RVZ) vs. left ventricular impedance (LVZ) for the case ofsynchrony between right and left ventricular contractions.

FIG. 4B is a graph (corresponding to FIG. 3B) of right ventricularimpedance (RVZ) vs. left ventricular impedance (LVZ) for the case ofmild asynchrony between right and left ventricular contractions.

FIG. 4C is a graph (corresponding to FIG. 3C) of right ventricularimpedance (RVZ) vs. left ventricular impedance (LVZ) for the case ofsevere asynchrony between right and left ventricular contractions.

FIG. 5A is a schematic illustration of another useful electrodeconfiguration that can be used in conjunction with the techniquesdescribed above with respect to FIGS. 1 and 2.

FIG. 5B is a schematic illustration of yet another useful electrodeconfiguration that can be used in conjunction with the techniquesdescribed above with respect to FIGS. 1 and 2.

FIG. 6 is a schematic diagram illustrating generally one example ofportions of a system and portions of an environment with which it isused.

FIG. 7 is a flow chart illustrating generally one example of a techniquefor determining a degree of synchrony or asynchrony between left andright ventricular contractions of a heart.

FIG. 8 is a conceptualized (not real data) signal diagram illustratingan embodiment in which a time window is established for identifying animpedance artifact.

FIG. 9 is a graph of phase delay vs. AV delay.

FIG. 10 is a schematic diagram illustrating generally one example ofportions of a system and portions of an environment with which it isused.

FIG. 11 is a flow chart illustrating generally one example of atechnique for controlling a cardiac resynchronization therapy (CRT)parameter in a way that tends to increase an impedance-based indicationof peak-to-peak volume (PV) or (dV/dt)_(max).

FIG. 12A is a graph of peak-to-peak volume (PV) vs. AV Delay.

FIG. 12B is a graph of (dV/dt)_(max) vs. AV Delay.

FIG. 13 is a conceptualized (not real data) signal diagram illustratingan embodiment in which a time window is established for measuring thepeak-to-peak volume (PV) or (dV/dt)_(max).

FIG. 14 is a schematic diagram illustrating generally one example ofportions of a system and portions of an environment with which it isused.

FIG. 15 is a flow chart illustrating generally one example of atechnique for determining a degree of synchrony or asynchrony betweenseptal and left ventricular freewall portions of a heart.

FIG. 16 is a conceptualized (not real data) signal diagram illustratingan embodiment in which a time window is established for identifying animpedance artifact.

FIG. 17 is a graph of phase delay vs. AV delay.

DETAILED DESCRIPTION

The following detailed description includes references to theaccompanying drawings, which form a part of the detailed description.The drawings show, by way of illustration, specific embodiments in whichthe invention may be practiced. These embodiments, which are alsoreferred to herein as “examples,” are described in enough detail toenable those skilled in the art to practice the invention. Theembodiments may be combined, other embodiments may be utilized, orstructural, logical and electrical changes may be made without departingfrom the scope of the present invention. The following detaileddescription is, therefore, not to be taken in a limiting sense, and thescope of the present invention is defined by the appended claims andtheir equivalents.

In this document, the terms “a” or “an” are used, as is common in patentdocuments, to include one or more than one. In this document, the term“or” is used to refer to a nonexclusive or, unless otherwise indicated.Furthermore, all publications, patents, and patent documents referred toin this document are incorporated by reference herein in their entirety,as though individually incorporated by reference. In the event ofinconsistent usages between this document and those documents soincorporated by reference, the usage in the incorporated reference(s)should be considered supplementary to that of this document; forirreconcilable inconsistencies, the usage in this document controls.

The present inventors have recognized a need for improved techniquesfor, among other things, determining the degree of asynchrony betweenthe left and right sides of the heart of a CHF patient. For example,techniques that detect electrical depolarizations (e.g., QRS complexes)at the left and right sides of the heart to indicate the synchronybetween the two sides of the heart are often not a good indicator of theactual mechanical synchrony between left and right ventricular heartcontractions. Another technique, for example, uses a pressure sensor todetermine synchrony between left and right ventricular contractions.However, such a pressure-sensing technique typically requires acustomized intracardiac lead that specially includes a pressure sensor.This adds expense and complexity to an implantable cardiac functionmanagement system.

This document describes, among other things, examples of cardiacfunction management systems, devices, and methods that measure animpedance, such as to determine or infer synchrony between right andleft ventricles, or to provide another control parameter for adjustingcardiac resynchronization (CRT) therapy. In further examples, theimpedance-derived information is used to automatically adjust one ormore cardiac resynchronization therapy (CRT) parameters, such as on abeat-by-beat basis in a closed-loop feedback configuration, to provideimproved spatial coordination of heart contractions (without necessarilyaffecting the actual heart rate of such heart contractions). The CRTtherapy typically improves ventricular mechanical synchrony, strokevolume, coordination, etc. by manipulating the electrical activationsequence, such as by delivering appropriate stimulations to desiredlocations.

EXAMPLE 1

FIG. 1 is a schematic diagram illustrating generally one example ofportions of a system 100 and portions of an environment with which it isused, including a heart 102. In this example, the system 100 includes animplantable cardiac function management device 104. In one example, thedevice 104 is coupled to the heart 102 using one or more intravascularor other leadwires. The leadwires provide electrodes 106 in associationwith the heart 102. FIG. 1 illustrates an example that includes a firstelectrode 106A that is located at or near a right ventricular freewall,a second electrode 106B that is located at or near a right ventricularseptum, a third electrode 106C that is located at or near a leftventricular septum, and a fourth electrode 106D that is located at ornear a left ventricular freewall. This particular electrodeconfiguration of FIG. 1 is useful for providing conceptual clarity,however, other possibly more practical electrode configurations will bediscussed further below.

In FIG. 1, device 104 includes an impedance circuit 108 for measuring afirst impedance indicative of right ventricular volume (e.g., betweenthe first electrode 106A and the second electrode 106B) and a secondimpedance indicative of a left ventricular volume (e.g., between thethird electrode 106C and the fourth electrode 106D). The first andsecond impedances are modulated as the right and left ventriclescontract and expand. In one example, this impedance modulation is usedto detect asynchrony between the left and right ventricular heartcontractions, as discussed below.

In the example of FIG. 1, a depolarization detector circuit 110 detectsintrinsic electrical heart depolarizations, such as by using one or moresense amplifiers 112 or signal processing circuits 114 to detect QRScomplexes, which are depolarizations corresponding to ventricular heartcontractions. The time interval between two successive QRS complexes canbe used to define a cardiac cycle. In one example, the impedancemodulation is monitored over a cardiac cycle for making the asynchronydetermination, as discussed below.

In the example of FIG. 1, a microprocessor, microcontroller, or otherprocessor circuit 116 executes, interprets, or otherwise performsinstructions to provide computational ability. The impedance circuit 108provides a sampled data right ventricular impedance waveform Z₁(n) and asampled data left ventricular impedance waveform Z₂(n) to the processor116 to be stored in a memory circuit 118 located within or external tothe processor 116. In one example, the processor 116 uses a cardiaccycle's worth of the right ventricular impedance waveform Z₁(n) and ofthe left ventricular impedance waveform Z₂(n) to compute an indicationof the degree of asynchrony (or, conversely, of synchrony) between theright and left ventricles, as discussed below. In one example, thisindication is provided by a synchrony fraction (SF) computation module120 comprising instructions that are executed by the processor 116. In afurther example, the SF or other indication of asynchrony or synchronyis used to control at least one cardiac resynchronization therapy (CRT)parameter 122. The CRT parameter 122, in turn, controls one or moreaspects of the delivery of stimulation pulses or other CRT therapy bytherapy circuit 124, which is coupled to electrodes associated with theheart 102, such as electrodes 106 or other electrodes.

Impedance measurement circuit 108 can be implemented in a number ofdifferent ways, such as by using circuits and techniques similar tothose used for detecting transthoracic impedance, an example of which isdescribed in Hartley et al. U.S. Pat. No. 6,076,015, which isincorporated herein by reference in its entirety, including itsdescription of impedance measurement. The Hartley et al. U.S. Pat. No.6,076,015 describes, among other things, injecting a four-phase carriersignal through two electrodes, such as the present electrodes 106A-B, orthe present electrodes 106C-D. Hartley et al. uses first and thirdphases that are +320 microampere pulses, which are 20 microseconds long.The second and fourth phases are −320 microampere pulses that are 20microseconds long. The four phases are repeated at 50 millisecondintervals to provide a carrier test current signal from which aresponsive voltage can be measured. However, different excitationfrequency, amplitude, and pulse duration can also be used. Theseimpedance testing parameters are typically selected to be subthreshold,that is, they use an energy that avoids evoking a responsive heartcontraction. These impedance testing parameters are also typicallyselected to avoid introducing a visible artifact on an ECG signalmonitor of intrinsic heart signals.

The Hartley et al. U.S. Pat. No. 6,076,015 describes a suitable excitercircuit for delivering such a test current stimulus (however, thepresent system can alternatively use other suitable circuits, includingan arbitrary waveform generator that is capable of operating atdifferent frequencies or of mixing different frequencies to generate anarbitrary waveform). It also describes a suitable signal processingcircuit for measuring a responsive voltage, such as between the presentelectrodes 106A-B, or between the present electrodes 106C-D. In oneexample, the signal processing circuit includes a preamplifier,demodulator, and bandpass filter for extracting the impedance data fromthe carrier signal, before conversion into digital form by an A/Dconverter. Further processing is performed digitally, and is typicallyperformed differently in the present system 100 than in the Hartley etal. U.S. Pat. No. 6,076,015. For example, the present system typicallyincludes a digital filter that passes frequency components of themeasured impedance signal that are close to the frequency of heartcontractions. The present digital filter typically attenuates otherlower or higher frequency components of the measured impedance signal.

FIG. 2 is a flow chart illustrating generally one example of a techniquefor determining a degree of synchrony or asynchrony between left andright ventricular contractions of a heart. At 200A, a right ventricularimpedance (“RVZ” or “Z₁”) is monitored over a cardiac cycle, such as byinjecting a subthreshold (i.e., non-contraction-evoking) current andmeasuring a responsive voltage (e.g., using electrodes 106A-B).Concurrent with 200A, at 200B, a left ventricular impedance (“LVZ” or“Z₂”) is monitored over the same cardiac cycle, such as by injecting asubthreshold current and measuring a responsive voltage (e.g., usingelectrodes 106C-D).

FIGS. 3A, 3B, and 3C are conceptual (not real data) impedance vs. timegraphs of RVZ and LVZ over the same cardiac cycle for the respectivecases of synchrony, mild asynchrony, and severe asynchrony between rightand left ventricular contractions. Corresponding to FIGS. 3A, 3B, and3C, respectively, are the Lissajous graphs of FIGS. 4A, 4B, and 4C,which plot right ventricular impedance (RVZ) vs. left ventricularimpedance (LVZ) for the respective cases of synchrony, mild asynchrony,and severe asynchrony between right and left ventricular contractions.As illustrated in FIGS. 4A, 4B, and 4C, as asynchrony increases, aninterior loop area 400 swept by RVZ vs. LVZ over the cardiac cycleincreases (e.g., from approximately zero in FIG. 4A for the case ofsynchrony).

At 202 in FIG. 2, the interior loop area 400 (as illustrated in FIG. 4)is calculated or approximated. A larger interior loop area indicates alarger degree of asynchrony. However, this value can be “normalized,” ifdesired, such as described below with respect to 204 and 206. At 204, aZZ Rectangle Area is calculated as(LVZ_(maximum)−LVZ_(minimum))×(RVZ_(maximum)−RVZ_(minimum)).LVZ_(maximum) and LVZ_(minimum) are the respective maximum and minimumvalues of LVZ during the cardiac cycle. RVZ_(maximum)−RVZ_(minimum) arethe respective maximum and minimum values of RVZ during the same cardiaccycle.

At 206, a synchrony fraction (SF) is computed as (ZZ Rectangle Area−ZZLoop Area)÷(ZZ Rectangle Area). SF provides an indication of synchronybetween right and left ventricular contractions. In theory, completeasynchrony is indicated by SF=0 and perfect synchrony is indicated bySF=1. For example, FIG. 4A illustrates SF=1, FIG. 4B illustrates SF=0.5,and FIG. 4C illustrates SF=0.2. Thus, SF provides an intuitive measureof mechanical synchrony, similar to using the commonly known ejectionfraction (EF) measure of cardiac pumping function. Alternatively, anasynchrony fraction (ASF) could be computed as (1−SF). Because of theabove “normalization,” the SF is independent of absolute measurements ofintracardiac impedance and, therefore, should not require anypatient-specific calibration.

In one example, the SF, ASF, or other indication of synchrony orasynchrony is used in a closed loop system to adjust the value of one ormore CRT parameters to increase SF or decrease ASF. Examples of CRTparameters that can be varied to improve synchrony include, among otherthings: particular cardiac electrode site(s), atrioventricular (AV)delay, interventricular delay, or intraventricular delay.

In another example, the SF, ASF, or other indication of synchrony orasynchrony is communicated from the implantable device 104 to a local orremote external device 126, such as by using a telemetry circuit 128included within the implantable device 104. The indication can bedisplayed to physician or other caregiver, such as on a computer monitorportion of the external device 126.

In another example, the SF, ASF, or other indication of synchrony orasynchrony triggers a warning when the degree of asynchrony exceeds aparticular threshold value. In one example, the warning is communicatedto the external device 126, as described above. In another example, thewarning is communicated directly to the patient, such as by providing anaudible, vibrating, or other warning indicator within the implantabledevice 104.

FIG. 1 illustrated an example of an electrode configuration that isparticularly useful for conceptualizing how impedance can be correlatedto right and left ventricular volumes. However, other electrodeconfigurations can also be used in conjunction with the techniquesdescribed above with respect to FIGS. 1 and 2. In one such electrodeconfiguration, the electrodes 106B and 106C are merged into a commonseptal electrode. FIGS. 5A and 5B are schematic illustrations of someother useful electrode configurations that can be used in conjunctionwith the techniques described above with respect to FIGS. 1 and 2.

In FIG. 5A, the implantable device 104 is coupled to the heart 102 usinga first lead 500 that includes a right ventricular electrode 502Alocated at or near the right ventricular apex. The lead 500 (or,alternatively, a separate right atrial lead) also includes a rightatrial electrode 502B. In FIG. 5A, the implantable device 104 is alsocoupled to the heart 102 using a second lead 504 that extends into thecoronary sinus 506 and into a coronary sinus vein 508 such that itsdistal electrode 510A is located in the coronary sinus vein 508 inassociation with the left ventricular freewall. The example of FIG. 5Aapproximates right ventricular volume using a right ventricularimpedance (RVZ) obtained between the right atrial electrode 502B and theright ventricular electrode 502A. The example of FIG. 5A approximatesleft ventricular volume using a left ventricular impedance (LVZ)obtained between right atrial electrode 502B and left ventricularelectrode 510A. This electrode configuration is practical because itpotentially makes use of existing electrodes available with existingleads, however, it may be confounded slightly by other effects, such asright atrial volume fluctuations arising from right atrial contractions.

FIG. 5B is similar to FIG. 5A, however, FIG. 5B includes an additionalelectrode 510B on the coronary sinus lead 504. The electrode 510B islocated in the mid coronary sinus at a location that is closer to theleft atrium. The example of FIG. 5B approximates right ventricularvolume using a right ventricular impedance (RVZ) obtained between theright atrial electrode 502B and the right ventricular electrode 502A.The example of FIG. 5B approximates left ventricular volume using a leftventricular impedance (LVZ) obtained between left atrial electrode 510Band left ventricular electrode 510A. This electrode configuration ispractical because it potentially makes use of existing electrodesavailable with existing leads, however, it may be confounded slightly byother effects, such as right atrial volume fluctuations arising fromright atrial contractions. However, this electrode configurationprovides a global indication of left and right side synchrony orasynchrony, including atrial effects.

The example described above with respect to FIGS. 1-5B increases the SFby adjusting AV delay or other CRT parameter that improves the spatialcoordination of heart contractions without necessarily affecting thecardiac rate. However, as the cardiac rate changes (e.g., from thepatient exercising), adjusting the AV delay or other CRT parameter in aclosed-loop fashion on a beat-by-beat basis may increase the SF at suchother heart rates. These techniques are expected to be useful for CHFpatients with or without electrical conduction disorder, because theyfocus on a control parameter that is not derived from intrinsicelectrical heart signals, but instead use impedance indicative of amechanical contraction parameter. For this reason, these techniques arealso particularly useful for a patient with complete AV block, in whichintrinsic electrical signals are not conducted to the ventricles and,therefore, CRT control techniques involving QRS width or otherelectrical parameters would be unavailable. For similar reasons, thesetechniques are useful even for patients who manifest a narrow QRS width,for whom QRS width would not be effective as a CRT control parameter.

EXAMPLE 2

FIG. 6 is a schematic diagram illustrating generally one example ofportions of a system 600 and portions of an environment with which it isused, including a heart 602. In this example, the system 600 includes animplantable cardiac function management device 604. In one example, thedevice 604 is coupled to the heart 602 using one or more intravascularor other leads. The leads provide electrodes 606 in association with theheart 602. FIG. 6 illustrates an example that includes a first electrode606A that is located at or near an midportion of a right ventricularfreewall, a second electrode 606B that is located in association with aleft ventricular freewall, such as by being introduced on anintravascular lead that is inserted into coronary sinus 607 toward acoronary sinus vein. A third electrode 606C is located on ahermetically-sealed housing (“can”) of the implantable device 604 (or,alternatively, on an insulating “header” extending from the housing ofthe implantable device 604).

In FIG. 6, the device 604 includes an impedance circuit 608 formeasuring a right ventricular impedance between the first electrode 606Aand the third electrode 606C and a left ventricular impedance betweenthe second electrode 606B and the third electrode 606C. The right andleft ventricular impedances are modulated as the right and leftventricles contract and expand. In one example, this impedancemodulation is used to detect asynchrony between the left and rightventricular heart contractions, as discussed below.

In the example of FIG. 6, a depolarization detector circuit 610 detectsintrinsic electrical heart depolarizations, such as by using one or moresense amplifiers 612 or signal processing circuits 614 to detect QRScomplexes, which are depolarizations corresponding to ventricular heartcontractions. The time interval between two successive QRS complexes canbe used to define a cardiac cycle. In one example, the impedancemodulation is monitored over all or a particular desired portion of acardiac cycle for making the asynchrony determination, as discussedbelow.

In the example of FIG. 6, a microprocessor, microcontroller, or otherprocessor circuit 616 executes instructions to provide computationalability. The impedance circuit 608 provides a sampled data rightventricular impedance waveform Z₁(n) and a sampled data left ventricularimpedance waveform Z₂(n) to the processor 616 to be stored in a memorycircuit 618 located within or external to the processor 616. In oneexample, the processor 616 samples at least a portion of a cardiaccycle's worth of the right ventricular impedance waveform Z₁(n) and ofthe left ventricular impedance waveform Z₂(n) to compute an indicationof the degree of asynchrony (or, conversely, of synchrony) between theright and left ventricles, as discussed below. In one example, thisindication is provided by a phase difference (PD) computation module 620comprising instructions that are executed by the processor 616. In afurther example, the PD or other indication of asynchrony or synchronyis used to control at least one cardiac resynchronization therapy (CRT)parameter 622. The CRT parameter 622, in turn, controls one or moreaspects of the delivery of stimulation pulses or other CRT therapy bytherapy circuit 624, which is coupled to electrodes associated with theheart 602, such as electrodes 606 or other electrodes.

Impedance measurement circuit 608 can be implemented in a number ofdifferent ways, such as by using circuits and techniques similar tothose used for detecting transthoracic impedance, an example of which isdescribed in Hartley et al. U.S. Pat. No. 6,076,015, which isincorporated herein by reference in its entirety, including itsdescription of impedance measurement. The Hartley et al. U.S. Pat. No.6,076,015 describes, among other things, injecting a four-phase carriersignal through two electrodes, such as the present electrodes 606A and606C, or the present electrodes 606B and 606C. Hartley et al. uses firstand third phases that are +320 microampere pulses, which are 20microseconds long. The second and fourth phases are −320 microamperepulses that are 20 microseconds long. The four phases are repeated at 50millisecond intervals to provide a carrier test current signal fromwhich a responsive voltage can be measured. However, differentexcitation frequency, amplitude, and pulse duration can also be used.These impedance testing parameters are typically selected to besubthreshold, that is, to avoid evoking a responsive heart contraction.These impedance testing parameters are also typically selected to avoidintroducing a visible artifact on an ECG signal monitor.

The Hartley et al. U.S. Pat. No. 6,076,015 describes an exciter circuitfor delivering such a test current stimulus (however, the present systemcan alternatively use other suitable circuits, including an arbitrarywaveform generator that is capable of operating at different frequenciesor of mixing different frequencies to generate an arbitrary waveform).It also describes a signal processing circuit for measuring a responsivevoltage, such as between the present electrodes 606A and 606C, orbetween the present electrodes 606B and 606C. In one example, the signalprocessing circuit includes a preamplifier, demodulator, and bandpassfilter for extracting the impedance data from the carrier signal, beforeconversion into digital form by an A/D converter. Further processing isperformed digitally, and is performed differently in the present system600 than in the Hartley et al. U.S. Pat. No. 6,076,015. The impedancecircuit 608 of the present system typically includes a digital filterthat passes frequency components of the measured impedance signal thatare close to the frequency of heart contractions. The digital filtertypically attenuates other lower or higher frequency components of themeasured impedance signal.

FIG. 7 is a flow chart illustrating generally one example of a techniquefor determining a degree of synchrony or asynchrony between left andright ventricular contractions of a heart. At 700A, a right ventricularimpedance (RVZ) is monitored over a cardiac cycle, such as by injectinga subthreshold (i.e., non-contraction-evoking) current (e.g., betweenelectrodes 606A and 606C) and measuring a responsive voltage (e.g.,using electrodes 606A and 606C). Concurrent with 700A, at 700B, a leftventricular impedance (LVZ) is monitored over the same cardiac cycle,such as by injecting a subthreshold current (e.g., between electrodes606B and 606C) and measuring a responsive voltage (e.g., usingelectrodes 606B and 606C).

At 702, a phase difference (PD) between the right and left ventricularcontractions is calculated using the RVZ and LVZ. In one embodiment, thephase difference is calculated by measuring a time difference betweenthe same artifact on each of the RVZ and LVZ signals. In one example, azero-cross detector detects a like zero-crossing artifact in each of theRVZ and LVZ signals, and PD is then calculated as the time differencebetween occurrences of these two like zero-crossings. In anotherexample, a peak-detector detects a like peak artifact in each of the RVZand LVZ signals, and PD is then calculated as the time differencebetween occurrences of these two like peaks. In yet another example, alevel-detector detects a like level in each of the RVZ and LVZ signals,and PD is then calculated as a time difference between the occurrencesof these two like signal levels.

In one embodiment, in order to better identify a like impedance artifactin each of the RVZ and LVZ signals for obtaining the phase difference,the zero-crossing, peak-detect, level-detect, etc. is performed during aparticular time window portion of the cardiac cycle. In one example,this is accomplished by establishing such a time window relative to aQRS complex or other electrical artifact as detected by thedepolarization detector 610, as illustrated in the conceptualized (notreal data) signal diagram of FIG. 8. In FIG. 8, a time window between t₁and t₂ is triggered following predetermined delay from a ventricularsense (V_(S)) QRS complex or ventricular pace at time t₀. During thetime window, the LVZ and RVZ are examined for the occurrence of aparticular impedance artifact. In the illustrated conceptual example,the impedance artifact is an LVZ falling below a certain threshold valueZ_(L) (which occurs, in this example, at time t₄) and a correspondingRVZ falling below a corresponding threshold value Z_(R) (which occurs,in this example, at time t₃). In this example, the PD magnitude is t₄−t₃with RVZ leading.

In FIG. 7, at 704 if PD indicates that the right ventricle is leading bymore than a threshold value (PDT+), then at 706, the AV delay isshortened by a small incremental value, which tends to reduce the amountby which the right ventricle leads the left ventricle. Otherwise, at708, if the PD indicates that the left ventricle is leading by more thana threshold value (PDT−), then at 710, the AV delay is lengthened by asmall incremental value, which tends to reduce the amount by which theleft ventricle leads the right ventricle. Otherwise, at 712, if neitherthe right nor left ventricles is leading by more than its respectivethreshold, then the AV delay is left unchanged, which tends to leave thesynchrony between the left and right ventricles unchanged. The behaviorof 704-712 is further understood by reference to the phase delay vs. AVdelay graph of FIG. 9. Using PD as an error signal in a closed loopsystem to control a CRT parameter (such as AV Delay), FIG. 9 illustrateshow synchrony between the left and right ventricles is promoted.

Although FIGS. 7 and 9 illustrate AV delay as the particular CRTparameter being modified to effect closed-loop control reducing PD,other CRT parameters could similarly be modified to reduce PD. Anotherexample of a CRT parameter is LV offset (LVO), which is the differencebetween a right ventricular AV delay (AVDR) and a left ventricular AVdelay (AVDL). More particularly, LVO=AVDL−AVDR. Therefore, a positiveLVO indicates that the right ventricle is programmed to be stimulatedearlier than the left ventricle; a negative LVO indicates that the leftventricle is programmed to be stimulated earlier than the rightventricle. In one example, the LVO is adjusted in a closed-loop fashionto reduce the PD error signal, in a similar manner to that illustratedin FIGS. 7 and 9. Similarly, other CRT parameter(s) can be adjusted in aclosed-loop fashion to reduce the PD error signal and improve right andleft ventricular mechanical synchrony.

The example described above with respect to FIGS. 6-9 reduces the PD byadjusting AV delay or other CRT parameter that improves the spatialcoordination of heart contractions without necessarily affecting thecardiac rate. However, as the cardiac rate changes (e.g., from thepatient exercising), adjusting the AV delay or other CRT parameter in aclosed-loop fashion on a beat-by-beat basis may reduce the PD at suchother heart rates. These techniques are expected to be useful for CHFpatients with or without electrical conduction disorder, because theyfocus on a control parameter that is not derived from intrinsicelectrical heart signals, but instead use impedance indicative of amechanical contraction parameter. For this reason, these techniques arealso particularly useful for a patient with complete AV block, in whichintrinsic electrical signals are not conducted to the ventricles and,therefore, CRT control techniques involving QRS width or otherelectrical parameters would be unavailable. For similar reasons, thesetechniques are useful even for patients who manifest a narrow QRS width,for whom QRS width would not be effective as a CRT control parameter.

EXAMPLE 3

FIG. 10 is a schematic diagram illustrating generally one example ofportions of a system 1000 and portions of an environment with which itis used, including a heart 1002. In this example, the system 1000includes an implantable cardiac function management device 1004. In oneexample, the device 1004 is coupled to the heart 1002 using one or moreintravascular or other leads. The leads provide electrodes 1006 inassociation with the heart 1002. FIG. 10 illustrates an example thatincludes a first electrode 1006A that is located at or near a middle orapical portion of a right ventricular septum, a second electrode 1006Bthat is located in association with a left ventricular freewall, such asby being introduced on an intravascular lead that is inserted intocoronary sinus 1007 toward a lateral or posterior coronary sinus vein.

In FIG. 10, the device 1004 includes an impedance circuit 1008 formeasuring a left ventricular impedance between the first electrode 1006Aand the second electrode 1006B. The left ventricular impedance ismodulated as the left ventricle contracts and expands. In one example,this impedance modulation is used to control a cardiac resynchronizationtherapy (CRT) parameter, as discussed below.

In the example of FIG. 10, a depolarization detector circuit 1010detects intrinsic electrical heart depolarizations, such as by using oneor more sense amplifiers 1012 or signal processing circuits 1014 todetect QRS complexes, which are depolarizations corresponding toventricular heart contractions. The time interval between two successiveQRS complexes can be used to define a cardiac cycle. In one example, theimpedance modulation is monitored over all or a particular desiredportion of a cardiac cycle for making the asynchrony determination, asdiscussed below.

In the example of FIG. 10, a microprocessor, microcontroller, or otherprocessor circuit 1016 executes instructions to provide computationalability. The impedance circuit 1008 provides a sampled data ventricularimpedance waveform Z₁(n) to the processor 1016 to be stored in a memorycircuit 1018 located within or external to the processor 1016. In thisillustrative example, the sampled data ventricular impedance waveformZ₁(n) is a left ventricular impedance. However, it is understood thatthis technique could alternatively be implemented using a rightventricular impedance waveform Z₁(n).

In one example, the processor 1016 samples a cardiac cycle's worth ofthe left ventricular impedance waveform Z₁(n) to compute one or both of:(1) an impedance-indicated peak-to-peak volume (PV) indication of theleft ventricle; or (2) an impedance-indicated maximum rate of change inleft ventricular volume ((dV/dt)_(max)), as discussed below. In oneexample, the PV or (dV/dt)_(max) is provided by a peak volume (PV) or(dV/dt)_(max) computation module 1020 comprising instructions that areexecuted by the processor 1016. In a further example, the PV or(dV/dt)_(max) is used to control at least one cardiac resynchronizationtherapy (CRT) parameter 1022 such that it tends to increase PV or(dV/dt)_(max). The CRT parameter 1022, in turn, controls one or moreaspects of the delivery of stimulation pulses or other CRT therapy bytherapy circuit 1024, which is coupled to electrodes associated with theheart 1002, such as electrodes 1006 or other electrodes.

Impedance measurement circuit 1008 can be implemented in a number ofdifferent ways, such as by using circuits and techniques similar tothose used for detecting transthoracic impedance, an example of which isdescribed in Hartley et al. U.S. Pat. No. 6,076,015, which isincorporated herein by reference in its entirety, including itsdescription of impedance measurement. The Hartley et al. U.S. Pat. No.6,076,015 describes, among other things, injecting a four-phase carriersignal through two electrodes, such as the present electrodes 1006A and1006B. Hartley et al. uses first and third phases that are +320microampere pulses, which are 20 microseconds long. The second andfourth phases are −320 microampere pulses that are 20 microseconds long.The four phases are repeated at 50 millisecond intervals to provide acarrier test current signal from which a responsive voltage can bemeasured. However, different excitation frequency, amplitude, and pulseduration can also be used. These impedance testing parameters aretypically selected to be subthreshold, that is, to avoid evoking aresponsive heart contraction. These impedance testing parameters arealso typically selected to avoid introducing a visible artifact on anECG signal monitor.

The Hartley et al. U.S. Pat. No. 6,076,015 describes an exciter circuitfor delivering such a test current stimulus (however, the present systemcan alternatively use other suitable circuits, including an arbitrarywaveform generator that is capable of operating at different frequenciesor of mixing different frequencies to generate an arbitrary waveform).It also describes a signal processing circuit for measuring a responsivevoltage, such as between the present electrodes 1006A and 1006B. In oneexample, the signal processing circuit includes a preamplifier,demodulator, and bandpass filter for extracting the impedance data fromthe carrier signal, before conversion into digital form by an A/Dconverter. Further processing is performed digitally, and is performeddifferently in the present system 1000 than in the Hartley et al. U.S.Pat. No. 6,076,015. The impedance circuit 1008 of the present systemtypically includes a digital filter that passes frequency components ofthe measured impedance signal that are close to the frequency of heartcontractions. The digital filter typically attenuates other lower orhigher frequency components of the measured impedance signal.

FIG. 11 is a flow chart illustrating generally one example of atechnique for controlling a cardiac resynchronization therapy (CRT)parameter in a way that tends to increase an impedance-based indicationof PV or (dV/dt)_(max). At 1100, a left ventricular impedance (LVZ) ismonitored over a cardiac cycle, such as by injecting a subthreshold(i.e., non-contraction-evoking) current (e.g., between electrodes1006A-B) and measuring a responsive voltage (e.g., using electrodes1006A-B).

At 1102, a peak-to-peak volume (PV) or (dV/dt)_(max) is calculated usingthe LVZ signal. At 1104 one of the (PV) or (dV/dt)_(max) is compared toits corresponding value for the previous cardiac cycle. If the currentvalue equals or exceeds the previous value, then at 1106 the current AVdelay is compared to an AV delay from the previous cardiac cycle (or anaveraged or filtered value over several such prior cardiac cycles). If,at 1106, the current AV delay equals or exceeds the previous AV delay,then at 1108, the AV delay is lengthened slightly for the next cardiaccycle and process flow returns to 1100. Otherwise, at 1106, if thecurrent AV delay is less than the previous AV delay, then the AV delayis shortened slightly at 1109 for the next cardiac cycle and processflow returns to 1100.

At 1104, if the current value is less than the previous value, then at1110. The current AV delay is compared to an AV delay from the previouscardiac cycle (or an averaged or filtered value over several such priorcardiac cycles). If, at 1110, the current AV delay equals or exceeds theprevious AV delay, then the AV delay is shortened slightly for the nextcardiac cycle at 1109 and process flow returns to 1100. Otherwise, at1110, if the current AV delay is less than the previous AV delay, thenat 1108 the AV delay is lengthened slightly for the next cardiac cycleand process flow returns to 1100.

Thus, in the example of FIG. 11, a CRT parameter such as AV delay isadjusted in such a way that it tends to increase PV or (dV/dt)_(max), asillustrated conceptually in the graphs of FIGS. 12A and 12B. In anotherembodiment, the CRT parameter is adjusted in such a way that it tends toincrease a weighted measure of both PV and (dV/dt)_(max). Similarly,other CRT parameter(s) can be adjusted in a closed-loop fashion toincrease PV or (dV/dt)_(max). In FIG. 11, each condition(current=previous) can alternatively be associated with (current<previous), instead of being associated with (current >previous), asindicated in the example of FIG. 11.

In one embodiment, in order to better identify the desired controlparameter(s) PV or (dV/dt)_(max), the peak-to-peak or slope measurementis performed during a particular time window portion of the cardiaccycle. In one example, this is accomplished by establishing such a timewindow relative to a QRS complex or other electrical artifact asdetected by the depolarization detector 1010, as illustrated in theconceptualized (not real data) signal diagram of FIG. 13. In FIG. 13, atime window between t₁ and t₂ is triggered following predetermined delayfrom a ventricular sense (V_(S)) QRS complex or ventricular pace (V_(P))at time t₀. During the time window, the LVZ limits the time period formeasuring the control parameter PV or (dV/dt)_(max). In the illustratedconceptual example, the PV is measured between times t₃ and t₄, whichcorrespond to maximum and minimum values of the LVZ, respectively.

EXAMPLE 4

FIG. 14 is a schematic diagram illustrating generally one example ofportions of a system 1400 and portions of an environment with which itis used, including a heart 1402. In this example, the system 1400includes an implantable cardiac function management device 1404. In oneexample, the device 1404 is coupled to the heart 1402 using one or moreintravascular or other leads. The leads provide electrodes 1406 inassociation with the heart 1402. FIG. 14 illustrates an example thatincludes a first electrode 1406A that is located at or near a midportionof a right ventricular septum, a second electrode 1406B that is locatedin association with a left ventricular freewall, such as by beingintroduced on an intravascular lead that is inserted into coronary sinus1407 toward a coronary sinus vein. A third electrode 1406C is located ona hermetically-sealed housing (“can”) of the implantable device 1404(or, alternatively, on an insulating “header” extending from the housingof the implantable device 1404).

In FIG. 14, the device 1404 includes an impedance circuit 1408 formeasuring a first impedance between the first electrode 1406A and thethird electrode 1406C and a second impedance between the secondelectrode 1406B and the third electrode 1406C). The first and secondimpedances are modulated as the septum and freewall portions of the leftventricle contract and expand. In one example, this impedance modulationis used to detect asynchrony between two different locations associatedwith the left ventricle, as discussed below.

In the example of FIG. 14, a depolarization detector circuit 1410detects intrinsic electrical heart depolarizations, such as by using oneor more sense amplifiers 1412 or signal processing circuits 1414 todetect QRS complexes, which are depolarizations corresponding toventricular heart contractions. The time interval between two successiveQRS complexes can be used to define a cardiac cycle. In one example, theimpedance modulation is monitored over all or a particular desiredportion of a cardiac cycle for making the asynchrony determination, asdiscussed below.

In the example of FIG. 14, a microprocessor, microcontroller, or otherprocessor circuit 1416 executes instructions to provide computationalability. The impedance circuit 1408 provides a sampled data firstventricular impedance waveform Z₁(n) and a sampled data secondventricular impedance waveform Z₂(n) to the processor 1416 to be storedin a memory circuit 1418 located within or external to the processor1416. In one example, the processor 1416 samples at least a portion of acardiac cycle's worth of the first ventricular impedance waveform Z₁(n)and of the second ventricular impedance waveform Z₂(n) to compute anindication of the degree of asynchrony (or, conversely, of synchrony)between the first (e.g., septal) and second (e.g., freewall) portions ofthe left ventricle, as discussed below. In one example, this indicationis provided by a phase difference (PD) computation module 1420comprising instructions that are executed by the processor 1416. In afurther example, the PD or other indication of asynchrony or synchronyis used to control at least one cardiac resynchronization therapy (CRT)parameter 1422. The CRT parameter 1422, in turn, controls one or moreaspects of the delivery of stimulation pulses or other CRT therapy bytherapy circuit 1424, which is coupled to electrodes associated with theheart 1402, such as electrodes 1406 or other electrodes.

Impedance measurement circuit 1408 can be implemented in a number ofdifferent ways, such as by using circuits and techniques similar tothose used for detecting transthoracic impedance, an example of which isdescribed in Hartley et al. U.S. Pat. No. 6,076,015, which isincorporated herein by reference in its entirety, including itsdescription of impedance measurement. The Hartley et al. U.S. Pat. No.6,076,015 describes, among other things, injecting a four-phase carriersignal through two electrodes, such as the present electrodes 1406A and1406C, or the present electrodes 1406B and 1406C. Hartley et al. usesfirst and third phases that are +320 microampere pulses, which are 20microseconds long. The second and fourth phases are −320 microamperepulses that are 20 microseconds long. The four phases are repeated at 50millisecond intervals to provide a carrier test current signal fromwhich a responsive voltage can be measured. However, differentexcitation frequency, amplitude, and pulse duration can also be used.These impedance testing parameters are typically selected to besubthreshold, that is, to avoid evoking a responsive heart contraction.These impedance testing parameters are also typically selected to avoidintroducing a visible artifact on an ECG signal monitor.

The Hartley et al. U.S. Pat. No. 6,076,015 describes an exciter circuitfor delivering such a test current stimulus (however, the present systemcan alternatively use other suitable circuits, including an arbitrarywaveform generator that is capable of operating at different frequenciesor of mixing different frequencies to generate an arbitrary waveform).It also describes a signal processing circuit for measuring a responsivevoltage, such as between the present electrodes 1406A and 1406C, orbetween the present electrodes 1406B and 1406C. In one example, thesignal processing circuit includes a preamplifier, demodulator, andbandpass filter for extracting the impedance data from the carriersignal, before conversion into digital form by an A/D converter. Furtherprocessing is performed digitally, and is performed differently in thepresent system 1400 than in the Hartley et al. U.S. Pat. No. 6,076,015.The impedance circuit 1408 of the present system typically includes adigital filter that passes frequency components of the measuredimpedance signal that are close to the frequency of heart contractions.The digital filter typically attenuates other lower or higher frequencycomponents of the measured impedance signal.

FIG. 15 is a flow chart illustrating generally one example of atechnique for determining a degree of synchrony or asynchrony betweenfirst and second locations of left ventricular contractions of a heart.At 1500A, a first ventricular impedance (Z₁) is monitored over a cardiaccycle, such as by injecting a subthreshold (i.e.,non-contraction-evoking) current (e.g., between electrodes 1406A and1406C) and measuring a responsive voltage (e.g., using electrodes 1406Aand 1406C). Concurrent with 1500A, at 1500B, a second ventricularimpedance (Z₂) is monitored over the same cardiac cycle, such as byinjecting a subthreshold current (e.g., between electrodes 1406B and1406C) and measuring a responsive voltage (e.g., using electrodes 1406Band 1406C).

At 1502, a phase difference (PD) between the first and second locationsof the ventricular contractions is calculated using Z₁ and Z₂. In oneembodiment, the phase difference is calculated by measuring a timedifference between the same artifact on each of the Z₁ and Z₂ signals.In one example, a zero-cross detector detects a like zero-crossingartifact in each of the Z₁ and Z₂ signals, and PD is then calculated asthe time difference between occurrences of these two likezero-crossings. In another example, a peak-detector detects a like peakartifact in each of the Z₁ and Z₂ signals, and PD is then calculated asthe time difference between occurrences of these two like peaks. In yetanother example, a level-detector detects a like level in each of the Z₁and Z₂ signals, and PD is then calculated as a time difference betweenthe occurrences of these two like signal levels.

In one embodiment, in order to better identify a like impedance artifactin each of the Z₁ and Z₂ signals for obtaining the phase difference, thezero-crossing, peak-detect, level-detect, etc. is performed during aparticular time window portion of the cardiac cycle. In one example,this is accomplished by establishing such a time window relative to aQRS complex or other electrical artifact as detected by thedepolarization detector 1410, as illustrated in the conceptualized (notreal data) signal diagram of FIG. 16. In FIG. 16, a time window betweent₁ and t₂ is triggered following predetermined delay from a ventricularsense (V_(S)) QRS complex or ventricular pace at time t₀. During thetime window, the Z₁ and Z₂ signals are examined for the occurrence of aparticular impedance artifact. In the illustrated conceptual example,the impedance artifact is an Z₂ falling below a certain threshold valueZ_(2T) (which occurs, in this example, at time t₄) and a correspondingZ₁ falling below a corresponding threshold value ZIT (which occurs, inthis example, at time t₃). In this example, the PD magnitude is t₄−t₃with Z₁ (septum) leading Z₂ (LV freewall).

In FIG. 15, at 1504 if PD indicates that Z₁ (the septum) is leading Z₂(the left ventricular freewall) by more than a threshold value (PDT+),then at 1506, the AV delay is shortened by a small incremental value,which tends to reduce the amount by which the septum leads the leftventricular freewall. Otherwise, at 1508, if the PD indicates that Z₂(the left ventricular freewall) is leading Z₁ (the septum) by more thana threshold value (PDT−), then at 1510, the AV delay is lengthened by asmall incremental value, which tends to reduce the amount by which theleft ventricular freewall leads the septum. Otherwise, at 1512, ifneither Z₁ (septum) or Z₂ (left ventricular freewall) is leading by morethan its respective threshold, then the AV delay is left unchanged,which tends to leave the synchrony between the septum and the leftventricular freewall unchanged. The behavior of 1504-1512 is furtherunderstood by reference to the phase delay vs. AV delay graph of FIG.17. Using PD as an error signal in a closed loop system to control a CRTparameter (such as AV Delay), FIG. 17 illustrates how synchrony betweenthe septum and left ventricular freewall is promoted.

Although FIGS. 15 and 17 illustrate AV delay as the particular CRTparameter being modified to effect closed-loop control reducing PD,other CRT parameters could similarly be modified to reduce PD. Anotherexample of a CRT parameter is LV offset (LVO), which is the differencebetween a right ventricular AV delay (AVDR) and a left ventricular AVdelay (AVDL). More particularly, LVO=AVDL−AVDR. Therefore, a positiveLVO indicates that the right ventricle is programmed to be stimulatedearlier than the left ventricle; a negative LVO indicates that the leftventricle is programmed be stimulated earlier than the right ventricle.In one example, the LVO is adjusted in a closed-loop fashion to reducethe PD error signal between the septum and the left ventricularfreewall, in a similar manner to that illustrated in FIGS. 15 and 17.Similarly, other CRT parameter(s) can be adjusted in a closed-loopfashion to reduce the PD error signal and improve right and leftventricular mechanical synchrony.

The example described above with respect to FIGS. 14-17 reduces the PDby adjusting AV delay or other CRT parameter that improves the spatialcoordination of heart contractions without necessarily affecting thecardiac rate. However, as the cardiac rate changes (e.g., from thepatient exercising), adjusting the AV delay or other CRT parameter in aclosed-loop fashion on a beat-by-beat basis may reduce the PD at suchother heart rates. These techniques are expected to be useful for CHFpatients with or without electrical conduction disorder, because theyfocus on a control parameter that is not derived from intrinsicelectrical heart signals, but instead use impedance indicative of amechanical contraction parameter. For this reason, these techniques arealso particularly useful for a patient with complete AV block, in whichintrinsic electrical signals are not conducted to the ventricles and,therefore, CRT control techniques involving QRS width or otherelectrical parameters would be unavailable. For similar reasons, thesetechniques are useful even for patients who manifest a narrow QRS width,for whom QRS width would not be effective as a CRT control parameter.

CONCLUSION

Portions of the above description have emphasized using LVZ to determinethe control parameter. This is because, in most CHF patients,enlargement occurs in the left ventricle, and therefore, cardiacresynchronization therapy is most effective when used to help controlleft ventricular cardiac output. However, in some patients, enlargementoccurs in the right ventricle instead of the left ventricle. For suchpatients, the cardiac resynchronization techniques described above canbe applied analogously to the right ventricle, or to both ventricles.

At least some of the examples described above with improve the strokevolume of a ventricle by adjusting AV delay or other CRT parameter thatimproves the spatial coordination of heart contractions withoutnecessarily affecting the cardiac rate. However, as the cardiac ratechanges (e.g., from the patient exercising), adjusting the AV delay orother CRT parameter in a closed-loop fashion on a beat-by-beat basis mayimprove the stroke volume at such other heart rates. These techniquesare expected to be useful for CHF patients with or without electricalconduction disorder, because they focus on a control parameter that isnot derived from intrinsic electrical heart signals, but instead useimpedance indicative of a mechanical contraction parameter. For thisreason, these techniques are also particularly useful for a patient withcomplete AV block, in which intrinsic electrical signals are notconducted to the ventricles and, therefore, CRT control techniquesinvolving QRS width or other electrical parameters would be unavailable.For similar reasons, these techniques are useful even for patients whomanifest a narrow QRS width, for whom QRS width would not be effectiveas a CRT control parameter.

Although the above examples have emphasized beat-by-beat closed-loopcontrol of CRT parameters, it is understood that such techniques arealso applicable to providing useful information to a physician or othercaregiver to help guide the appropriate programming of one or more CRTparameters.

The accompanying drawings that form a part hereof, show by way ofillustration, and not of limitation, specific embodiments in which thesubject matter may be practiced. The embodiments illustrated aredescribed in sufficient detail to enable those skilled in the art topractice the teachings disclosed herein. Other embodiments may beutilized and derived therefrom, such that structural and logicalsubstitutions and changes may be made without departing from the scopeof this disclosure. This Detailed Description, therefore, is not to betaken in a limiting sense, and the scope of various embodiments isdefined only by the appended claims, along with the full range ofequivalents to which such claims are entitled.

Such embodiments of the inventive subject matter may be referred toherein, individually and/or collectively, by the term “invention” merelyfor convenience and without intending to voluntarily limit the scope ofthis application to any single invention or inventive concept if morethan one is in fact disclosed. Thus, although specific embodiments havebeen illustrated and described herein, it should be appreciated that anyarrangement calculated to achieve the same purpose may be substitutedfor the specific embodiments shown. This disclosure is intended to coverany and all adaptations, or variations, or combinations of variousembodiments. Combinations of the above embodiments, and otherembodiments not specifically described herein, will be apparent to thoseof skill in the art upon reviewing the above description.

The Abstract of the Disclosure is provided to comply with 37 C.F.R.§1.72(b), requiring an abstract that will allow the reader to quicklyascertain the nature of the technical disclosure. It is submitted withthe understanding that it will not be used to interpret or limit thescope or meaning of the claims. In addition, in the foregoing DetailedDescription, it can be seen that various features are grouped togetherin a single embodiment for the purpose of streamlining the disclosure.This method of disclosure is not to be interpreted as reflecting anintention that the claimed embodiments require more features than areexpressly recited in each claim. Rather, as the following claimsreflect, inventive subject matter lies in less than all features of asingle disclosed embodiment. Thus the following claims are herebyincorporated into the Detailed Description, with each claim standing onits own as a separate embodiment.

It is to be understood that the above description is intended to beillustrative, and not restrictive. For example, the above-describedembodiments (and/or aspects thereof) may be used in combination witheach other. Many other embodiments will be apparent to those of skill inthe art upon reviewing the above description. The scope of the inventionshould, therefore, be determined with reference to the appended claims,along with the full scope of equivalents to which such claims areentitled. In the appended claims, the terms “including” and “in which”are used as the plain-English equivalents of the respective terms“comprising” and “wherein.” Also, in the following claims, the terms“including” and “comprising” are open-ended, that is, a system, device,article, or process that includes elements in addition to those listedafter such a term in a claim are still deemed to fall within the scopeof that claim. Moreover, in the present document, including in thefollowing claims, the terms “first,” “second,” and “third,” etc. areused merely as labels, and are not intended to impose numericalrequirements on their objects.

1. A machine-assisted method comprising: measuring a first impedancesignal, the first impedance signal indicative of a volume of a firstventricle of a heart as the first ventricle expands and contracts duringa cardiac cycle; using the first impedance signal to measure a maximumrate of change of volume of the first ventricle during a systole portionof a cardiac cycle; and automatically adjusting, using the maximum rateof change of volume, at least one cardiac resynchronization therapyparameter that synchronizes left and right ventricular heartcontractions, the automatically adjusting tending to increase themaximum rate of change in the volume over at least one subsequentcardiac cycle.
 2. The method of claim 1, in which the first ventricle isa left ventricle, and in which measuring the first impedance signalincludes: injecting a current through at least a portion of the leftventricle; and measuring a responsive voltage between a first electrodelocated at an apex of a right ventricle and a second electrodeintroduced into at least one of a coronary sinus and great cardiac veinin association with the left ventricle.
 3. The method of claim 1, inwhich the automatically adjusting at least one cardiac resynchronizationtherapy parameter includes adjusting an atrioventricular (AV) delay. 4.The method of claim 1, in which the automatically adjusting at least onecardiac resynchronization therapy parameter includes adjusting a leftventricular offset.
 5. The method of claim 1, in which the automaticallyadjusting at least one cardiac resynchronization therapy parameterincludes adjusting an intraventricular delay.
 6. The method of claim 1,in which the automatically adjusting at least one cardiacresynchronization therapy parameter includes adjusting aninterventricular delay.
 7. The method of claim 1, in which theautomatically adjusting at least one cardiac resynchronization therapyparameter includes lengthening an atrioventricular delay if either: (1)the first impedance signal indicates that a current cardiac cycle'smaximum rate of change in the volume is less than a previous cardiaccycle's maximum rate of change in the volume and a current cardiaccycle's atrioventricular delay is less than a previous cardiac cycle'satrioventricular delay; or (2) the first impedance signal indicates thata current cardiac cycle's maximum rate of change in the volume isgreater than or equal to a previous cardiac cycle's maximum rate ofchange in the volume and a current cardiac cycle's atrioventriculardelay is greater than or equal to a previous cardiac cycle'satrioventricular delay.
 8. The method of claim 7, in which theautomatically adjusting at least one cardiac resynchronization therapyparameter includes shortening an atrioventricular delay if either: (1)the first impedance signal indicates that a current cardiac cycle'smaximum rate of change in the volume is less than a previous cardiaccycle's maximum rate of change in the volume and a current cardiaccycle's atrioventricular delay is greater than or equal to a previouscardiac cycle's atrioventricular delay; or (2) the first impedancesignal indicates that a current cardiac cycle's maximum rate of changein the volume is greater than or equal to a previous cardiac cycle'smaximum rate of change in the volume and a current cardiac cycle'satrioventricular delay is less than a previous cardiac cycle'satrioventricular delay.
 9. The method of claim 1, in which theautomatically adjusting at least one cardiac resynchronization therapyparameter includes shortening an atrioventricular delay if either: (1)the first impedance signal indicates that a current cardiac cycle'smaximum rate of change in the volume is less than a previous cardiaccycle's maximum rate of change in the volume and a current cardiaccycle's atrioventricular delay is greater than or equal to a previouscardiac cycle's atrioventricular delay; or (2) the first impedancesignal indicates that a current cardiac cycle's maximum rate of changein the volume is greater than or equal to a previous cardiac cycle'smaximum rate of change in the volume and a current cardiac cycle'satrioventricular delay is less than a previous cardiac cycle'satrioventricular delay.
 10. The method of claim 1, in which the usingthe first impedance signal to measure a maximum rate of change in thevolume includes: detecting a cardiac depolarization; and constrainingthe measurement of maximum rate of change in the volume to occur duringa time window measured from a cardiac depolarization.
 11. The method ofclaim 1, further comprising communicating data indicative of the maximumrate of change in the volume from an implantable cardiac functionmanagement device.
 12. The method of claim 11, further comprisingdisplaying an indication representative of information about the maximumrate of change in the volume using an external device.
 13. A systemcomprising: an implantable cardiac function management devicecomprising: an impedance measurement circuit, including terminalsconfigured to be coupled to electrodes for association with a firstventricle of a heart to measure an impedance signal to determine avolume of the first ventricle during a cardiac cycle of the heart; and aprocessor circuit, coupled to the impedance measurement circuit toreceive information about the impedance signal, the processor configuredto execute or interpret instructions to measure a maximum rate of changein volume of the first ventricle during a systole portion of the cardiaccycle, the processor further configured to execute or interpretinstructions to automatically adjust in a closed-loop manner, using themeasured maximum rate of change in the volume, a cardiacresynchronization therapy parameter that synchronizes left and rightventricular heart contractions in a manner that tends to increase themaximum rate of change in the volume during a subsequent cardiac cycle.14. The system of claim 13, in which the first ventricle is a leftventricle, and in which the system includes: first and second electrodesconfigured to inject a current through at least a portion of the leftventricle; and a third electrode positioned on an intracardiac lead tobe located at an apex of a right ventricle and a fourth electrode sizedand shaped on a lead to be introduced into at least one of a coronarysinus and a great cardiac vein in association with the left ventricle,the third and fourth electrodes configured for measuring a voltageresponsive to the injected current.
 15. The system of claim 14, in whichthe first and second electrodes are the same electrodes as the third andfourth electrodes, respectively.
 16. The system of claim 14, in whichthe processor is configured to execute or interpret instructions toautomatically adjust the at least one cardiac resynchronization therapyparameter by adjusting an atrioventricular (AV) delay.
 17. The system ofclaim 14, in which the processor is configured to execute or interpretinstructions to automatically adjust the at least one cardiacresynchronization therapy parameter by adjusting a left ventricularoffset.
 18. The system of claim 14, in which the processor is configuredto execute or interpret instructions to automatically adjust the atleast one cardiac resynchronization therapy parameter by adjusting anintraventricular delay.
 19. The system of claim 14, in which theprocessor is configured to execute or interpret instructions toautomatically adjust the at least one cardiac resynchronization therapyparameter by adjusting an interventricular delay.
 20. The system ofclaim 14, in which the processor is configured to execute or interpretinstructions to automatically adjust the at least one cardiacresynchronization therapy parameter by lengthening an atrioventriculardelay if either: (1) the first impedance signal indicates that a currentcardiac cycle's maximum rate of change in the volume is less than aprevious cardiac cycle's maximum rate of change in the volume and acurrent atrioventricular delay is less than a previous cardiac cycle'satrioventricular delay; or (2) the first impedance signal indicates thata current cardiac cycle's maximum rate of change in the volume isgreater than or equal to a previous cardiac cycle's maximum rate ofchange in the volume and a current cardiac cycle's atrioventriculardelay is greater than or equal to a previous cardiac cycle'satrioventricular delay.
 21. The system of claim 20, in which theprocessor is configured to execute or interpret instructions toautomatically adjust the at least one cardiac resynchronization therapyparameter by shortening an atrioventricular delay if either: (1) thefirst impedance signal indicates that a current cardiac cycle's maximumrate of change in the volume is less than a previous cardiac cycle'smaximum rate of change in the volume and a current cardiac cycle'satrioventricular delay is greater than or equal to a previous cardiaccycle's atrioventricular delay; or (2) the first impedance signalindicates that a current cardiac cycle's maximum rate of change in thevolume is greater than or equal to a previous cardiac cycle's maximumrate of change in the volume and a current cardiac cycle'satrioventricular delay is less than a previous cardiac cycle'satrioventricular delay.
 22. The system of claim 14, in which theprocessor is configured to execute or interpret instructions toautomatically adjust the at least one cardiac resynchronization therapyparameter by shortening an atrioventricular delay if either: (1) thefirst impedance signal indicates that a current cardiac cycle's maximumrate of change in the volume is less than a previous cardiac cycle'smaximum rate of change in the volume and a current cardiac cycle'satrioventricular delay is greater than or equal to a previous cardiaccycle's atrioventricular delay; or (2) the first impedance signalindicates that a current cardiac cycle's maximum rate of change in thevolume is greater than or equal to a previous cardiac cycle's maximumrate of change in the volume and a current cardiac cycle'satrioventricular delay is less than a previous cardiac cycle'satrioventricular delay.
 23. The system of claim 14, in which theimplantable cardiac function management device includes a depolarizationdetector to detect a cardiac depolarization, and in which the processoris configured to execute or interpret instructions to constrain themeasurement of the maximum rate of change in the volume to occur duringa time window measured from a cardiac depolarization.
 24. The system ofclaim 14, in which the implantable cardiac function management deviceincludes a telemetry circuit configured for communicating dataindicative of the maximum rate of change in the volume from theimplantable cardiac function management device.
 25. The system of claim24, further comprising an external device including a monitor configuredto display an indication of the maximum rate of change in the volume.